A comparison of the effects of chronic "classical" and "atypical" neuroleptic treatments on a number of pre- and postsynaptic dopaminergic parameters in different regions of rat brain is proposed. Initial studies have shown that chronic haloperidol treatment results in tolerance to DOPAC elevation and tyrosine hydroxylase activation in some but not all brain regions studied (frontal cortex, corpus striatum, mesolimbic region, substantia nigra) when measured shortly after cessation of treatment. However, the development of tolerance in those regions which display this effect is dependent on drug dosage and treatment duration. During the withdrawal or supersensitivity period after termination of treatment these parameters are normal in all brain regions. Tolerance development does not occur in substantia nigra. Rather, DOPAC levels increase in this region. This effect, as well as the striatal tolerance, can also be elicited during the supersensitivity phase on re-challenge with haloperidol. These initial studies provide a "baseline" compilation of data inasmuch as haloperidol is a prototype "classical" neuroleptic. Experiments are in progress to extend such observations to "atypical" drugs such as clozapine and sulpiride. Deviations from the "baseline" profile may yield important clues to mechanistic differences between the different neuroleptics. Furthermore, these studies are expected to provide new insights to such phenomena as tolerance development, dopamine receptor sensitivity changes and tardive dyskinesia.